Demonstrators included antiwar group Jewish Voice for Peace, which said around 90 people were detained. Among those detained was whistleblower Chelsea Manning, a former US Army soldier and WikiLeaks source, Reuters reported.
The New York City Police Department said there were "multiple" arrests but did not provide a number.
Clips from the protests showed a crowd gathering near the offices of US Senate Minority Leader Chuck Schumer and his Democratic colleague, Senator Kirsten Gillibrand.
Protesters chanted slogans like "stop the bombs," "end the killings" and "free Palestine" while expressing opposition to the US-Israeli aggression on Iran, Israel's attacks in Lebanon and Israel's assault on Gaza.
The protesters also chanted "let Gaza live," "let Iran live" and "let Lebanon live."
The US and Israel attacked Iran on February 28. Iran responded with its own strikes on Israeli targets and US bases and assets in regional states. US-Israeli strikes on Iran and Israeli attacks in Lebanon have killed thousands and displaced millions.
US President Donald Trump's administration has cracked down on protests by attempting to deport foreign students, threatening to freeze funding for universities where protests were held and ordering screening of immigrants' online comments. The crackdown has faced judicial obstacles.
New York City was at the heart of pro-Palestinian protests in 2024.
US military support for Israel has faced particular scrutiny from rights groups during Israel's genocidal war in Gaza that killed tens of thousands, caused a hunger crisis, internally displaced Gaza's entire population and led to assessments of genocide from scholars and a United Nations inquiry.